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  1. Article ; Online: New Insights and Evidence on "Food Intolerances": Non-Celiac Gluten Sensitivity and Nickel Allergic Contact Mucositis.

    Greco, Nicoletta / Pisano, Annalinda / Mezzatesta, Laura / Pettinelli, Marta / Meacci, Arianna / Pignataro, Maria Gemma / Giordano, Carla / Picarelli, Antonio

    Nutrients

    2023  Volume 15, Issue 10

    Abstract: The clinical examination of patients often includes the observation of the existence of a close relationship between the ingestion of certain foods and the appearance of various symptoms. Until now, the occurrence of these events has been loosely defined ...

    Abstract The clinical examination of patients often includes the observation of the existence of a close relationship between the ingestion of certain foods and the appearance of various symptoms. Until now, the occurrence of these events has been loosely defined as food intolerance. Instead, these conditions should be more properly defined as adverse food reactions (AFRs), which can consist of the presentation of a wide variety of symptoms which are commonly identified as irritable bowel syndrome (IBS). In addition, systemic manifestations such as neurological, dermatological, joint, and respiratory disorders may also occur in affected patients. Although the etiology and pathogenesis of some of them are already known, others, such as non-celiac gluten sensitivity and adverse reactions to nickel-containing foods, are not yet fully defined. The study aimed to evaluate the relationship between the ingestion of some foods and the appearance of some symptoms and clinical improvements and detectable immunohistochemical alterations after a specific exclusion diet. One hundred and six consecutive patients suffering from meteorism, dyspepsia, and nausea following the ingestion of foods containing gluten or nickel were subjected to the GSRS questionnaire which was modified according to the "Salerno experts' criteria". All patients underwent detection of IgA antibodies to tissue transglutaminase, oral mucosal patch tests with gluten and nickel (OMPT), and EGDS, including biopsies. Our data show that GSRS and OMPT, the use of APERIO CS2 software, and the endothelial marker CD34 could be suggested as useful tools in the diagnostic procedure of these new pathologies. Larger, multi-center clinical trials could be helpful in defining these emerging clinical problems.
    MeSH term(s) Humans ; Food Intolerance/complications ; Nickel/adverse effects ; Mucositis/chemically induced ; Malabsorption Syndromes/complications ; Glutens/adverse effects ; Hypersensitivity ; Irritable Bowel Syndrome/etiology ; Celiac Disease/complications ; Diet, Gluten-Free
    Chemical Substances Nickel (7OV03QG267) ; Glutens (8002-80-0)
    Language English
    Publishing date 2023-05-17
    Publishing country Switzerland
    Document type Journal Article
    ZDB-ID 2518386-2
    ISSN 2072-6643 ; 2072-6643
    ISSN (online) 2072-6643
    ISSN 2072-6643
    DOI 10.3390/nu15102353
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  2. Article ; Online: PD-L1 testing in metastatic triple-negative breast cancer: Interobserver and interplatform reproducibility of CE-IVD assays for CPS and IC scores.

    Ivanova, Mariia / Frascarelli, Chiara / Cerbelli, Bruna / Pignataro, Maria Gemma / Pernazza, Angelina / Venetis, Konstantinos / Sajjadi, Elham / Criscitiello, Carmen / Curigliano, Giuseppe / Guerini-Rocco, Elena / Graziano, Paolo / Martini, Maurizio / d'Amati, Giulia / Fusco, Nicola

    Human pathology

    2024  Volume 144, Page(s) 22–27

    Abstract: PD-L1 test is recommended in different types of tumors to select patients eligible for immune checkpoint inhibitors (ICI) therapy. Several factors make this test challenging in metastatic triple-negative breast cancer (mTNBC). Different assays and ... ...

    Abstract PD-L1 test is recommended in different types of tumors to select patients eligible for immune checkpoint inhibitors (ICI) therapy. Several factors make this test challenging in metastatic triple-negative breast cancer (mTNBC). Different assays and platforms are available, each associated with distinct scoring systems and threshold values specific to the ICI compound used, i.e. CPS≥10 for pembrolizumab and IC ≥ 1 % for atezolizumab. Our objective was to assess the consistency of PD-L1 testing in mTNBC by examining interobserver and interassay reproducibility. We assessed n = 60 mTNBC samples for PD-L1 testing using 22C3 pharmDx assay on a Dako Autostainer Link 48 and VENTANA PD-L1 (SP263) on a Ventana BenchMark Ultra. Additionally, a subset of n = 19 samples was tested using the SP142 assay, also on the Ventana BenchMark Ultra. CPS with both 22C3 and SP263 was independently evaluated by five pathologists, all certified PD-L1 trainers. The IC with SP142 was assessed by three of these pathologists, who have particular expertise in breast pathology. Following the computation of the intraclass correlation coefficient (ICC) for each assay and their respective thresholds, we assessed the agreement between different raters and assays using Fleiss's κ, with a 95 % confidence interval (CI). Overall, we observed a significant (p < 0.001) ICC with both CPS assays [22C3 = 0.939 (CI:0.913-0.96); SP263 = 0.972 (CI:0.96-0.982); combined 22C3-SP263 = 0.909 (CI:0.874-0.938)]. Fleiss's κ confirmed an almost perfect agreement among pathologists and assays: 22C3 = 0.938 (CI:0.857-1.018); SP263 = 0.972 (CI:0.890-1.052); combined 22C3-SP263 = 0.907 (CI:0.869-0.945). Perfect inter-rater agreement was reached considering IC. This study establishes the reliability of assessing CPS in mTNBC using either the 22C3 pharmDx, as employed in the KEYNOTE studies, or the VENTANA SP263 assay. Each assay must be used on its designated platform, namely the Dako for 22C3 pharmDx and the Ventana for VENTANA SP263. It is important to remark that CPS and IC identify different patient cohorts and, therefore, are not interchangeable.
    MeSH term(s) Humans ; Reproducibility of Results ; Immunohistochemistry ; Triple Negative Breast Neoplasms/diagnosis ; B7-H1 Antigen ; Lung Neoplasms/pathology ; Biomarkers, Tumor
    Chemical Substances B7-H1 Antigen ; Biomarkers, Tumor
    Language English
    Publishing date 2024-01-24
    Publishing country United States
    Document type Journal Article
    ZDB-ID 207657-3
    ISSN 1532-8392 ; 0046-8177
    ISSN (online) 1532-8392
    ISSN 0046-8177
    DOI 10.1016/j.humpath.2024.01.008
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  3. Article ; Online: Atypical cellular neurothekeoma (ACN) of the elderly: case report and brief review of the literature.

    D'Alessandris, Nicoletta / Picchetto, Andrea / Pignataro, Maria Gemma / Cerbelli, Bruna / Manzo, Domenico / Rocca, Carlo Della / d'Amati, Giulia / Pernazza, Angelina

    Pathologica

    2021  Volume 112, Issue 4, Page(s) 210–213

    Abstract: Atypical cellular neurothekeoma (ACN) is an aggressive and rare variant of cellular neurothekeoma. Only few cases have been reported in the literature and the biological behavior seems to be uncertain. We describe the case of an ACN presenting on the ... ...

    Abstract Atypical cellular neurothekeoma (ACN) is an aggressive and rare variant of cellular neurothekeoma. Only few cases have been reported in the literature and the biological behavior seems to be uncertain. We describe the case of an ACN presenting on the scalp of an elderly man, emphasizing the cytologic features of malignancy. In addition, we provide a brief overview of the literature and discuss the differential diagnosis with other entities, and the possible diagnostic pitfalls.
    MeSH term(s) Aged ; Biomarkers, Tumor/analysis ; Diagnosis, Differential ; Humans ; Immunohistochemistry ; Male ; Neurothekeoma/diagnosis ; Neurothekeoma/pathology ; Scalp/pathology ; Skin Neoplasms/diagnosis ; Skin Neoplasms/pathology ; Soft Tissue Neoplasms/diagnosis ; Soft Tissue Neoplasms/pathology
    Chemical Substances Biomarkers, Tumor
    Language English
    Publishing date 2021-01-04
    Publishing country Italy
    Document type Case Reports
    ZDB-ID 418229-7
    ISSN 1591-951X ; 0031-2983
    ISSN (online) 1591-951X
    ISSN 0031-2983
    DOI 10.32074/1591-951X-104
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  4. Article ; Online: A new double immunohistochemistry method to detect mucosal anti-transglutaminase IgA deposits in coeliac children.

    Trovato, Chiara Maria / Oliva, Salvatore / Pietropaoli, Nicoletta / Pignataro, Maria Gemma / Berni, Silvia / Tancredi, Andrea / Cucchiara, Salvatore / Giordano, Carla / Montuori, Monica

    Digestive and liver disease : official journal of the Italian Society of Gastroenterology and the Italian Association for the Study of the Liver

    2021  Volume 54, Issue 2, Page(s) 200–206

    Abstract: Background: Intestinal transglutaminase (TG2) IgA deposits represent early marker of coeliac disease (CeD) and can predict the evolution towards intestinal atrophy.: Aims: To validate a double immunohistochemistry method for the determination of ... ...

    Abstract Background: Intestinal transglutaminase (TG2) IgA deposits represent early marker of coeliac disease (CeD) and can predict the evolution towards intestinal atrophy.
    Aims: To validate a double immunohistochemistry method for the determination of intestinal TG2 IgA deposits on formalin-fixed paraffin-embedded biopsies.
    Methods: Immunohistochemistry was tested on: 1) children with overt CeD [persistently positive serum IgA anti-tissue transglutaminase type 2 (TGA-IgA) with moderate or low titer, and histological findings of CeD]; 2) potential CeD (persistently positive serum TGA-IgA and normal intestinal mucosa) and 3) controls (negative serum TGA-IgA and normal intestinal mucosa).
    Results: Samples from 61 children were analyzed (32 overt CeD, 14 potential CeD, and 15 controls). Deposits appeared as focal, multifocal, or confluent extracellular foci of red and brown staining colocalization in the sub-epithelium and around mucosal vessels. Deposits were present in all 32 children with overt CeD and in 9/14 potential CeD. Deposits were never observed in the 15 controls. Patients with higher serum level of TGA-IgA and with mucosal atrophy showed mostly a multifocal/diffuse pattern of deposits distribution. The bulb appeared most severely involved. In potential CeD deposits showed mainly a focal distribution.
    Conclusion: Our results indicate double immunohistochemistry as promising diagnostic tool to improve diagnosis of CeD.
    MeSH term(s) Atrophy ; Autoantibodies/analysis ; Autoantibodies/blood ; Biomarkers/analysis ; Biopsy ; Celiac Disease/diagnosis ; Child ; Child, Preschool ; Female ; Humans ; Immunohistochemistry/methods ; Intestinal Mucosa/metabolism ; Intestinal Mucosa/pathology ; Male ; Predictive Value of Tests ; Reproducibility of Results
    Chemical Substances Autoantibodies ; Biomarkers ; anti-transglutaminase autoantibody
    Language English
    Publishing date 2021-11-26
    Publishing country Netherlands
    Document type Journal Article ; Validation Study
    ZDB-ID 1459373-7
    ISSN 1878-3562 ; 1125-8055
    ISSN (online) 1878-3562
    ISSN 1125-8055
    DOI 10.1016/j.dld.2021.11.006
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  5. Article: Molecular profiling of male breast cancer by multigene panel testing: Implications for precision oncology.

    Valentini, Virginia / Silvestri, Valentina / Bucalo, Agostino / Conti, Giulia / Karimi, Mina / Di Francesco, Linda / Pomati, Giulia / Mezi, Silvia / Cerbelli, Bruna / Pignataro, Maria Gemma / Nicolussi, Arianna / Coppa, Anna / D'Amati, Giulia / Giannini, Giuseppe / Ottini, Laura

    Frontiers in oncology

    2023  Volume 12, Page(s) 1092201

    Abstract: Introduction: Compared with breast cancer (BC) in women, BC in men is a rare disease with genetic and molecular peculiarities. Therapeutic approaches for male BC (MBC) are currently extrapolated from the clinical management of female BC, although the ... ...

    Abstract Introduction: Compared with breast cancer (BC) in women, BC in men is a rare disease with genetic and molecular peculiarities. Therapeutic approaches for male BC (MBC) are currently extrapolated from the clinical management of female BC, although the disease does not exactly overlap in males and females. Data on specific molecular biomarkers in MBC are lacking, cutting out male patients from more appropriate therapeutic strategies. Growing evidence indicates that Next Generation Sequencing (NGS) multigene panel testing can be used for the detection of predictive molecular biomarkers, including Tumor Mutational Burden (TMB) and Microsatellite Instability (MSI).
    Methods: In this study, NGS multigene gene panel sequencing, targeting 1.94 Mb of the genome at 523 cancer-relevant genes (TruSight Oncology 500, Illumina), was used to identify and characterize somatic variants, Copy Number Variations (CNVs), TMB and MSI, in 15 Formalin-Fixed Paraffin-Embedded (FFPE) male breast cancer samples.
    Results and discussion: A total of 40 pathogenic variants were detected in 24 genes. All MBC cases harbored at least one pathogenic variant.
    Language English
    Publishing date 2023-01-06
    Publishing country Switzerland
    Document type Journal Article
    ZDB-ID 2649216-7
    ISSN 2234-943X
    ISSN 2234-943X
    DOI 10.3389/fonc.2022.1092201
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  6. Article ; Online: Overexpression in metastatic breast cancer supports Syndecan-1 as a marker of invasiveness and poor prognosis.

    Cerbelli, Bruna / Pisano, Annalinda / Pignataro, Maria Gemma / Pernazza, Angelina / Botticelli, Andrea / Carosi, Mariantonia / Costarelli, Leopoldo / Allegretti, Matteo / d'Amati, Giulia / Cordone, Iole

    Clinical and experimental medicine

    2022  Volume 23, Issue 5, Page(s) 1641–1647

    Abstract: Background: Metastasis is the main cause of breast cancer (BC) mortality. Increasing evidence points to a role of syndecan-1 (CD138) expression as a prognostic marker involved in BC tissue and leptomeningeal metastasis. Aim of this study was to ... ...

    Abstract Background: Metastasis is the main cause of breast cancer (BC) mortality. Increasing evidence points to a role of syndecan-1 (CD138) expression as a prognostic marker involved in BC tissue and leptomeningeal metastasis. Aim of this study was to investigate and compare syndecan-1 tissue expression and localization in primary and secondary BC, focusing on brain metastases.
    Methods: Syndecan-1 expression was determined by immunohistochemistry. Focal vs diffuse (< or > 50% of cancer cells, respectively) pattern of expression, cellular localization (cytoplasm vs membrane) and intensity of immunostaining on neoplastic cells were evaluated. Moreover, the extent and pattern of expression of syndecan-1 were compared between primary tumors and paired metastases and correlated with the tumor intrinsic subtype.
    Results: A total of 23 cases, 10 with paired primary and metastatic tumor and 13 brain metastases, were evaluated. Syndecan-1 was expressed in both primary and metastatic BC. A diffuse cytoplasmic expression was observed in most primary BCs; by contrast, all metastatic lesions showed a membrane pattern of expression, suggesting a shift in cellular localization of syndecan-1 during the metastatic process. Concerning the extent of expression, we observed in metastatic lesions, a trend of association between intrinsic subtypes and extent of positivity. In particular, both BC characterized by overexpression of HER2 and triple-negative tumors were correlated with a diffuse pattern of expression with a moderate to strong intensity.
    Conclusion: A diffuse cytoplasmic expression was observed in most primary BCs; by contrast, all metastatic lesions showed a membrane pattern of expression, suggesting a shift in cellular localization of syndecan-1 during the metastatic process.
    MeSH term(s) Female ; Humans ; Biomarkers, Tumor/metabolism ; Brain Neoplasms ; Breast Neoplasms/pathology ; Immunohistochemistry ; Prognosis ; Syndecan-1/metabolism
    Chemical Substances Biomarkers, Tumor ; Syndecan-1 ; SDC1 protein, human
    Language English
    Publishing date 2022-09-10
    Publishing country Italy
    Document type Journal Article
    ZDB-ID 2053018-3
    ISSN 1591-9528 ; 1591-8890
    ISSN (online) 1591-9528
    ISSN 1591-8890
    DOI 10.1007/s10238-022-00880-7
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  7. Article: Clinical and histological features of patients with primary Sjögren's syndrome and autoimmune thyroiditis: a national multicentre cross-sectional study.

    Colafrancesco, Serena / Celia, Alessandra Ida / Baldini, Chiara / Quartuccio, Luca / Bartoloni, Elena / Carubbi, Francesco / Orlandi, Martina / Barbati, Cristiana / Pignataro, Maria Gemma / Cerbelli, Bruna / Giordano, Carla / Ferro, Francesco / Gattamelata, Angelica / Giardina, Federico / Izzo, Raffaella / Longhino, Simone / De Vita, Salvatore / Gerli, Roberto / Giacomelli, Roberto /
    Conti, Fabrizio / Priori, Roberta

    Clinical and experimental rheumatology

    2023  Volume 41, Issue 12, Page(s) 2389–2396

    Abstract: Objectives: Primary Sjögren's syndrome (pSS) is frequently associated with autoimmune thyroiditis (AT). The aim of this study was to evaluate the prevalence of AT in a national cohort of pSS and to describe the clinical and histological phenotype of ... ...

    Abstract Objectives: Primary Sjögren's syndrome (pSS) is frequently associated with autoimmune thyroiditis (AT). The aim of this study was to evaluate the prevalence of AT in a national cohort of pSS and to describe the clinical and histological phenotype of patients with pSS and associated AT.
    Methods: In this multicentre cross-sectional study, data from 2546 pSS were collected and the presence of AT was reported. In a subgroup, the histology of minor salivary glands was evaluated. Differences between pSS with and without AT were evaluated.
    Results: A concomitant pSS and AT was detected in 19.6% of cases. Patients with pSS and AT displayed a lower prevalence of lymphoma, male sex and disease-modifying anti-rheumatic drugs (DMARDs) use and a higher prevalence of fibromyalgia, coeliac disease and hypergammaglobulinaemia. Multivariable analysis confirmed a higher prevalence of fibromyalgia and coeliac disease and lower use of DMARDs. In a subgroup of patients (n=232), a significantly higher focus score and number of foci was detected in pSS without AT (n=169) as compared to pSS with AT (n=54).
    Conclusions: This is the largest study evaluating the coexistence of pSS and AT. We confirm a high association between pSS and AT and describe the presence of a different phenotype characterized by a higher rate of celiac disease and fibromyalgia. Although not significant, the lower prevalence of both lymphoma and intake of DMARDs, along with a significantly lower focus score and number of foci, possibly suggest a more favourable outcome in concomitant pSS and AT which further deserve future investigations.
    MeSH term(s) Humans ; Male ; Sjogren's Syndrome/complications ; Cross-Sectional Studies ; Fibromyalgia/diagnosis ; Fibromyalgia/epidemiology ; Fibromyalgia/complications ; Celiac Disease/complications ; Thyroiditis, Autoimmune/epidemiology ; Thyroiditis, Autoimmune/complications ; Thyroiditis, Autoimmune/drug therapy ; Antirheumatic Agents/therapeutic use ; Lymphoma
    Chemical Substances Antirheumatic Agents
    Language English
    Publishing date 2023-12-23
    Publishing country Italy
    Document type Multicenter Study ; Journal Article
    ZDB-ID 605886-3
    ISSN 1593-098X ; 0392-856X
    ISSN (online) 1593-098X
    ISSN 0392-856X
    DOI 10.55563/clinexprheumatol/eh36vs
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  8. Article ; Online: A multidisciplinary approach for the differential diagnosis between multiple primary lung adenocarcinomas and intrapulmonary metastases.

    Belardinilli, Francesca / Pernazza, Angelina / Mahdavian, Yasaman / Cerbelli, Bruna / Bassi, Massimiliano / Gradilone, Angela / Coppa, Anna / Pignataro, Maria Gemma / Anile, Marco / Venuta, Federico / Della Rocca, Carlo / Giannini, Giuseppe / d'Amati, Giulia

    Pathology, research and practice

    2021  Volume 220, Page(s) 153387

    Abstract: Purpose: The distinction between multiple primary lung cancers (MPLCs) and intrapulmonary metastases has a significant impact on tumor staging and therapeutic choices. Several criteria have been proposed to solve this diagnostic issue, but a definitive ... ...

    Abstract Purpose: The distinction between multiple primary lung cancers (MPLCs) and intrapulmonary metastases has a significant impact on tumor staging and therapeutic choices. Several criteria have been proposed to solve this diagnostic issue, but a definitive consensus is still missing. We tested the efficacy of a combined clinical, histopathological and molecular ("real world") approach for the correct classification of multiple lung tumors in a selected cohort of patients.
    Methods: 24 multiple lung tumors with a diagnosis of adenocarcinoma from 10 patients were retrospectively reviewed. Radiological, pathological and clinical information, including follow-up, were integrated with molecular profiling via a routine multigene panel sequencing.
    Results: Comprehensive histologic assessment revealed readily distinguishable histologic patterns between multiple tumors suggesting unrelated lesions in 7 cases, in agreement with clinical, radiological and molecular data, thus leading to final diagnosis of MPLCs. In the remaining 3 cases, the differential diagnosis between MPLCs and intrapulmonary metastases was challenging, since the histologic features of the lesions were similar or identical. The final interpretation (2 MPLCs and 1 most likely intrapulmonary metastases) was reached thanks to the integration of all available data, and was confirmed by follow-up.
    Conclusions: A multidisciplinary approach including a routinely affordable multigene panel sequencing is a useful tool to discriminate MPLCs from intrapulmonary metastases in multiple lung nodules sharing the adenocarcinoma histotype.
    MeSH term(s) Adenocarcinoma/diagnostic imaging ; Adenocarcinoma/genetics ; Adenocarcinoma/pathology ; Adenocarcinoma/secondary ; Adenocarcinoma of Lung/diagnostic imaging ; Adenocarcinoma of Lung/genetics ; Adenocarcinoma of Lung/pathology ; Aged ; Biomarkers, Tumor/genetics ; Biopsy ; Diagnosis, Differential ; Female ; Gene Expression Profiling ; High-Throughput Nucleotide Sequencing ; Humans ; Lung Neoplasms/diagnostic imaging ; Lung Neoplasms/genetics ; Lung Neoplasms/pathology ; Lung Neoplasms/secondary ; Male ; Middle Aged ; Neoplasms, Multiple Primary/diagnostic imaging ; Neoplasms, Multiple Primary/genetics ; Neoplasms, Multiple Primary/pathology ; Predictive Value of Tests ; Retrospective Studies ; Transcriptome
    Chemical Substances Biomarkers, Tumor
    Language English
    Publishing date 2021-02-17
    Publishing country Germany
    Document type Journal Article
    ZDB-ID 391889-0
    ISSN 1618-0631 ; 0344-0338
    ISSN (online) 1618-0631
    ISSN 0344-0338
    DOI 10.1016/j.prp.2021.153387
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  9. Article ; Online: Exogenous peptides are able to penetrate human cell and mitochondrial membranes, stabilize mitochondrial tRNA structures, and rescue severe mitochondrial defects.

    Perli, Elena / Pisano, Annalinda / Pignataro, Maria Gemma / Campese, Antonio Francesco / Pelullo, Maria / Genovese, Ilaria / de Turris, Valeria / Ghelli, Anna Maria / Cerbelli, Bruna / Giordano, Carla / Colotti, Gianni / Morea, Veronica / d'Amati, Giulia

    FASEB journal : official publication of the Federation of American Societies for Experimental Biology

    2020  Volume 34, Issue 6, Page(s) 7675–7686

    Abstract: Mutations in mitochondrial transfer RNA (mt-tRNA) genes are responsible for a wide range of syndromes, for which no effective treatment is available. We previously reported that transfection of the nucleotide sequence encoding for the 16-residue β32_33 ... ...

    Abstract Mutations in mitochondrial transfer RNA (mt-tRNA) genes are responsible for a wide range of syndromes, for which no effective treatment is available. We previously reported that transfection of the nucleotide sequence encoding for the 16-residue β32_33 peptide from mitochondrial leucyl-tRNA synthetase ameliorates the cell phenotype caused by the mitochondrial tRNA mutations. In this work, we demonstrated that both the β32_33 peptide linked with the known (L)-Phe-(D)-Arg-(L)-Phe-(L)-Lys (FrFK) mitochondrial penetrating sequence and, strikingly, the β32_33 peptide per se, are able to penetrate both the plasma and mitochondrial membranes and exert the rescuing activity when exogenously administered to cells bearing the mutations m.3243A > G and m.8344A > G. These mutations are responsible for the most common and severe mt-tRNA-related diseases. In addition, we dissected the molecular determinants of constructs activity by showing that both the order of amino acids along the sequence and presence of positive charges are essential determinants of the peptide activity in cells and mt-tRNA structures stabilization in vitro. In view of future in vivo studies, this information may be required to design of β32_33 peptide-mimetic derivatives. The β32_33 and FrFK-β32_33 peptides are, therefore, promising molecules for the development of therapeutic agents against diseases caused by the mt-tRNA point mutations.
    MeSH term(s) Amino Acids/metabolism ; Cell Line ; Humans ; Mitochondria/metabolism ; Mitochondrial Diseases/metabolism ; Mitochondrial Membranes/metabolism ; Peptides/metabolism ; Point Mutation/physiology ; RNA, Transfer/metabolism
    Chemical Substances Amino Acids ; Peptides ; RNA, Transfer (9014-25-9)
    Language English
    Publishing date 2020-04-18
    Publishing country United States
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 639186-2
    ISSN 1530-6860 ; 0892-6638
    ISSN (online) 1530-6860
    ISSN 0892-6638
    DOI 10.1096/fj.201903270R
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  10. Article ; Online: Circulating CD137+ T Cells Correlate with Improved Response to Anti-PD1 Immunotherapy in Patients with Cancer.

    Zizzari, Ilaria Grazia / Di Filippo, Alessandra / Botticelli, Andrea / Strigari, Lidia / Pernazza, Angelina / Rullo, Emma / Pignataro, Maria Gemma / Ugolini, Alessio / Scirocchi, Fabio / Di Pietro, Francesca Romana / Rossi, Ernesto / Gelibter, Alain / Schinzari, Giovanni / D'Amati, Giulia / Rughetti, Aurelia / Marchetti, Paolo / Nuti, Marianna / Napoletano, Chiara

    Clinical cancer research : an official journal of the American Association for Cancer Research

    2021  Volume 28, Issue 5, Page(s) 1027–1037

    Abstract: Purpose: CD137 molecule is expressed by activated lymphocytes, and in patients with cancer identifies the tumor-reactive T cells. In solid tumors, high levels of circulating CD137+ T cells are associated with the clinical response and the disease-free ... ...

    Abstract Purpose: CD137 molecule is expressed by activated lymphocytes, and in patients with cancer identifies the tumor-reactive T cells. In solid tumors, high levels of circulating CD137+ T cells are associated with the clinical response and the disease-free status. Here, we examined the role of the CD137+ T cells in the improvement of patients' selection for immunotherapy treatment.
    Experimental design: Peripheral blood mononuclear cells derived from 109 patients with metastatic cancer (66 patients for the identification cohort and 43 for the validation cohort) were analyzed for the expression of CD3, CD4, CD8, CD137, and PD1 molecules before the beginning of anti-PD1 therapy. Twenty healthy donors were used as control. The soluble form of CD137 (sCD137) was also analyzed. The CD137+ T cell subsets and the sCD137 were correlated with the clinicopathologic characteristics. The distribution of CD137+ T cells was also examined in different tumor settings.
    Results: The percentage of CD137+ T cells was higher in healthy donors and in those patients with a better clinical status (performance status = 0-1, n°metastasis≤2) and these high levels were ascribed to the CD8+CD137+ T cell population. The high frequency of CD137+ and CD8+CD137+ T cells resulted as a prognostic factor of overall survival (OS) and progression-free survival (PFS), respectively, and were confirmed in the validation cohort. High levels of CD3+CD137+PD1+ lymphocytes were associated with a low number of metastasis and longer survival. Instead, the high concentration of the immunosuppressive sCD137 in the serum is associated with a lower PFS and OS. In tumor bed, patients with a complete response showed a high percentage of CD137+ and CD8+ T cells.
    Conclusions: We propose the CD137+ T subset as an immune biomarker to define the wellness status of the immune system for successful anticancer immunotherapy.
    MeSH term(s) CD8-Positive T-Lymphocytes ; Humans ; Immunotherapy ; Leukocytes, Mononuclear/metabolism ; Lymphocyte Count ; Neoplasms/therapy ; Tumor Necrosis Factor Receptor Superfamily, Member 9
    Chemical Substances Tumor Necrosis Factor Receptor Superfamily, Member 9
    Language English
    Publishing date 2021-12-31
    Publishing country United States
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 1225457-5
    ISSN 1557-3265 ; 1078-0432
    ISSN (online) 1557-3265
    ISSN 1078-0432
    DOI 10.1158/1078-0432.CCR-21-2918
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